title: Assignment of the locus for PLO-SL, a frontal-lobe dementia with bone cysts, to 19q13.
abstract: PLO-SL (polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy) is a recessively inherited disorder characterized by systemic bone cysts and progressive presenile frontal-lobe dementia, resulting in death at <50 years of age. Since the 1960s, approximately 160 cases have been reported, mainly in Japan and Finland. The pathogenesis of the disease is unknown. In this article, we report the assignment of the locus for PLO-SL, by random genome screening using a modification of the haplotype-sharing method, in patients from a genetically isolated population. By screening five patient samples from 2 Finnish families, followed by linkage analysis of 12 Finnish families, 3 Swedish families, and 1 Norwegian family, we were able to assign the PLO-SL locus to a 9-cM interval between markers D19S191 and D19S420 on chromosome 19q13. The critical region was further restricted, to approximately 1.8 Mb, by linkage-disequilibrium analysis of the Finnish families. According to the haplotype analysis, one Swedish and one Norwegian PLO-SL family are not linked to the chromosome 19 locus, suggesting that PLO-SL is a heterogeneous disease. In this chromosomal region, one potential candidate gene for PLO-SL, the gene encoding amyloid precursor-like protein 1, was analyzed, but no mutations were detected in the coding region.
authors.affiliation: Department of Human Molecular Genetics, Institute of Biomedicine, University of Helsinki, Helsinki, Finland.
authors.forename: P
authors.initials: P
authors.lastname: Pekkarinen
authors.forename: I
authors.initials: I
authors.lastname: Hovatta
authors.forename: P
authors.initials: P
authors.lastname: Hakola
authors.forename: O
authors.initials: O
authors.lastname: Järvi
authors.forename: M
authors.initials: M
authors.lastname: Kestilä
authors.forename: U
authors.initials: U
authors.lastname: Lenkkeri
authors.forename: R
authors.initials: R
authors.lastname: Adolfsson
authors.forename: G
authors.initials: G
authors.lastname: Holmgren
authors.forename: P O
authors.initials: PO
authors.lastname: Nylander
authors.forename: L
authors.initials: L
authors.lastname: Tranebjaerg
authors.forename: J D
authors.initials: JD
authors.lastname: Terwilliger
authors.forename: J
authors.initials: J
authors.lastname: Lönnqvist
authors.forename: L
authors.initials: L
authors.lastname: Peltonen
mesh_terms: D000293:Adolescent; D000328:Adult; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D001845:Bone Cysts / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D003704:Dementia / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D005190:Family; D005260:Female; D005387:Finland / Q000453:epidemiology; D005625:Frontal Lobe; D005808:Genes, Recessive; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D015995:Prevalence
chemical_list: C489697:APLP1 protein, human; C084104:APLP2 protein, human; D016564:Amyloid beta-Protein Precursor; D005819:Genetic Markers; D009419:Nerve Tissue Proteins